A Low Viral Load Predicts a Higher Initial Virologic Response to Adefovir in Patients with Lamivudine-Resistant Chronic Hepatitis B
2
조회
0
다운로드
1
인용
0
참고문헌
초록
Background/Aims: Adefovir (ADV) is the preferred drug for treating lamivudine (LAM)-resistant hepatitis B. However, not all patients who face virologic breakthrough during LAM treatment respond to ADV. The aim of this study was to determine the factors associated with efficacy of ADV in LAM-resistant hepatitis B patients. Methods: The medical records of 231 patients who received ADV due to LAM-resistance were reviewed. Efficacy was assessed by the initial virologic response (IVR), defined as hepatitis B virus (HBV) DNA not being undetectable by real-time PCR at 6 months of ADV treatment. Results: Seventy patients (30%) achieved IVR. While ‘add-on’ modality,hepatitis B e antigen (HBeAg) negativity, and low baseline HBV DNA levels were associated with IVR in univariate analysis, multivariate analysis revealed HBeAg status and the DNA level to be the significant factors. The probability of IVR achievement increased sharply per each log10 copies/mL decrement in the baseline viral load, which was 133 times in patients who had HBV DNA ＜105 copies/mL compared with those who had ≥108 copies/mL. Conclusions: Factors associated with the IVR were HBeAg negativity and a low baseline viral load. Therefore, when virologic breakthrough with genotypic resistance emerges during LAM therapy, ADV treatment should be considered immediately before further increases in viral load. Additional long-term follow-up data are warranted
Abstract
Background/Aims: Adefovir (ADV) is the preferred drug for treating lamivudine (LAM)-resistant hepatitis B. However, not all patients who face virologic breakthrough during LAM treatment respond to ADV. The aim of this study was to determine the factors associated with efficacy of ADV in LAM-resistant hepatitis B patients. Methods: The medical records of 231 patients who received ADV due to LAM-resistance were reviewed. Efficacy was assessed by the initial virologic response (IVR), defined as hepatitis B virus (HBV) DNA not being undetectable by real-time PCR at 6 months of ADV treatment. Results: Seventy patients (30%) achieved IVR. While ‘add-on’ modality,hepatitis B e antigen (HBeAg) negativity, and low baseline HBV DNA levels were associated with IVR in univariate analysis, multivariate analysis revealed HBeAg status and the DNA level to be the significant factors. The probability of IVR achievement increased sharply per each log10 copies/mL decrement in the baseline viral load, which was 133 times in patients who had HBV DNA ＜105 copies/mL compared with those who had ≥108 copies/mL. Conclusions: Factors associated with the IVR were HBeAg negativity and a low baseline viral load. Therefore, when virologic breakthrough with genotypic resistance emerges during LAM therapy, ADV treatment should be considered immediately before further increases in viral load. Additional long-term follow-up data are warranted
참고문헌 (32)
- European Association for the Study of the Liver, "EASL Clinical Practice Guidelines: management of chronic hepatitis B", J Hepatol, 50, pp.227~242 (2009)
- Liaw YF, "Lamivudine for patients with chronic hepatitis B and advanced liver disease", N Engl J Med, 351, pp.1521~1531 (2004)
- Hadziyannis SJ, "Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years", Gastroenterology, 131, pp.1743~1751 (2006)
- Marcellin P, "Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B", Hepatology, 48, pp.750~758 (2008)
- Liaw YF, "Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update", Hepatol Int, 2, pp.263~283 (2008)
- Lok AS, "Chronic hepatitis B: update 2009", Hepatology, 50, pp.661~662 (2009)
- Fung SK, "Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation", J Hepatol, 43, pp.937~943 (2005)
- Lee JM, "Long-term adefovir dipivoxil monotherapy for up to 5 years in lamivudine-resistant chronic hepatitis B", Antivir Ther, 15, pp.235~241 (2010)
- 문재현, "라미부딘 내성 만성 B형간염 환자에서 아데포비어 단독치료의 효과와 아데포비어에 대한 유전자형 내성의 발생 양상", The Korean Journal of Hepatology, 14(4), pp.503~512 (2008), 대한간학회
- Rapti I, "Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B", Hepatology, 45, pp.307~313 (2007)
- Shin JW, "Precore stop codon mutation of hepatitis B virus is associated with low breakthrough rate following long-term lamivudine therapy", J Gastroenterol Hepatol, 20, pp.844~849 (2005)
- Yuen MF, "Significance of viral load, core promoter", precore mutations and specific sequences of polymerase gene in HBV-infected patients on 3-year lamivudine treatment, 2006, pp.11, 779~786
- Asahina Y, "Core promoter", pre-core mutations are associated with lamivudine-induced HBeAg loss in chronic hepatitis B with genotype C, 2003, pp.39, 1063~1069
- Kim HJ, "The prevalence and clinical significance of precore and core promoter mutations in Korean patients with chronic hepatitis B virus infection", Taehan Kan Hakhoe Chi, 8, pp.149~156 (2002)
- Yoo BC, "Precore and core promoter mutations of hepatitis B virus and hepatitis B e antigen-negative chronic hepatitis B in Korea", J Hepatol, 38, pp.98~103 (2003)
- Chang ML, "Virus and transaminase levels determine the emergence of drug resistance during long-term lamivudine therapy in chronic hepatitis B", J Hepatol, 43, pp.72~77 (2005)
- Nafa S, "Early detection of viral resistance by determination of hepatitis B virus polymerase mutations in patients treated by lamivudine for chronic hepatitis B", Hepatology, 32, pp.1078~1088 (2000)
- Yuen MF, "Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy", Hepatology, 34, pp.785~791 (2001)
- Kurashige N, "Factors contributing to antiviral effect of adefovir dipivoxil therapy added to ongoing lamivudine treatment in patients with lamivudine-resistant chronic hepatitis B", J Gastroenterol, 44, pp.601~607 (2009)
- Pellicelli AM, "Adefovir and lamivudine in combination compared with adefovir monotherapy in HBeAg-negative adults with chronic hepatitis B virus infection and clinical or virologic resistance to lamivudine: a retrospective, multicenter, nonrandomized, open-label study", Clin Ther, 30, pp.317~323 (2008)
- Chen CH, "Virological response and incidence of adefovir resistance in lamivudine-resistant patients treated with adefovir dipivoxil", Antivir Ther, 11, pp.771~778 (2006)
- Fung SK, "Virologic response and resistance to adefovir in patients with chronic hepatitis B", J Hepatol, 44, pp.283~290 (2006)
- Zollner B, "Correlation of hepatitis B virus load with loss of e antigen and emerging drug-resistant variants during lamivudine therapy", J Med Virol, 65, pp.659~663 (2001)
- Chan HL, "Treatment of hepatitis B e antigen positive chronic hepatitis with telbivudine or adefovir: a randomized trial", Ann Intern Med, 147, pp.745~754 (2007)
- Chan HL, "Early virological suppression is associated with good maintained response to adefovir dipivoxil in lamivudine resistant chronic hepatitis B", Aliment Pharmacol Ther, 25, pp.891~898 (2007)
- Liaw YF, "2-Year GLOBE trial results:telbivudine Is superior to lamivudine in patients with chronic hepatitis B", Gastroenterology, 136, pp.486~495 (2009)
- Reijnders JG, "Entecavir shows limited efficacy in HBeAg-positive hepatitis B patients with a partial virologic response to adefovir therapy", J Hepatol, 50, pp.674~683 (2009)
- Zeuzem S, "Baseline characteristics and early on-treatment response predict the outcomes of 2 years of telbivudine treatment of chronic hepatitis B", J Hepatol, 51, pp.11~20 (2009)
- Reijnders JG, "On-treatment monitoring of adefovir therapy in chronic hepatitis B: virologic response can be assessed at 24 weeks", J Viral Hepat, 16, pp.113~120 (2009)
- Lampertico P, "Low resistance to adefovir combined with lamivudine: a 3-year study of 145 lamivudine-resistant hepatitis B patients", Gastroenterology, 133, pp.1445~1451 (2007)
- Liaw YF, "Hepatitis B virus infection", Lancet, 373, pp.582~592 (2009)
- Lok AS, "Antiviral drug-resistant HBV: standardization of nomenclature and assays and recommendations for management", Hepatology, 46, pp.254~265 (2007)